Epigenetic modulation of the JAK2-STAT3 signaling pathway in osteoporosis: non-coding RNA networks as therapeutic targets.

BACKGROUND

Osteoporosis, a prevalent metabolic bone disease affects over 200 million people worldwide and is associated with an elevated fracture risk, is characterized by an imbalance between bone resorption and formation. The JAK2-STAT3 signaling pathway serves as a critical regulator of bone remodeling, but its chronic activation contributes to pathological bone metabolism in osteoporosis. Understanding the precise regulation of this pathway is essential for developing novel therapies.

MAIN BODY: Our review reveals that specific miRNAs directly target components of the JAK2-STAT3 pathway (e.g. JAK2, STAT3, SOCS) to fine-tune osteoblast and osteoclast activity. This regulatory network is further expanded by lncRNAs and circRNAs, which act as competitive endogenous RNAs (ceRNAs) or "molecular sponges" to sequester miRNAs, thereby indirectly modulating JAK2-STAT3 signaling. This multi-tiered ncRNA network influences key processes such as osteogenic differentiation, inflammatory response and mitochondrial redox homeostasis, ultimately determining bone metabolic balance.

CONCLUSION

The ncRNA network represents a promising therapeutic target for bone-related and metabolic diseases, especially osteoporosis, through its precise control over the JAK2-STAT3 pathway. Targeting these ncRNAs, potentially via engineered exosomes or biomaterial-based delivery systems, offers a novel and different strategy for restoring bone homeostasis, paving the way for future precision medicine in bone metabolic diseases.